The local Make Strides event will take place on Saturday, October 9, at Headwaters Park East.

For more information, click here.

As we treat people with chemotherapy, making them comfortable is paramount,” says Dan Konow, chief operating officer for Fort Wayne Medical Oncology and Hematology.

These new chairs are luxury-class chairs that feature heat and massage,” Konow continues. “Some patients may be in a chemotherapy chair for up to eight hours during a single treatment, and because of the nature of intravenous chemotherapy, many people tend to feel cold. We provide blankets, of course, but these new chairs really add an extra element of comfort. Many of our other chemotherapy chairs have built-in TVs and DVD players, but an increasing number of patients now request the new chairs because of the heat and massage features.

Fort Wayne Medical Oncology and Hematology has added three of the new chairs to its facility on the Parkview North campus, while the remaining four are at the practice’s facility on the Lutheran Hospital campus.

Of course, we’re very appreciative that Vera Bradley donated the money that’s enabling us to provide a little more comfort to our patients as they face the challenges of cancer and diseases of the blood,” Konow says.

Nemschoff, the company that makes the chairs, donates a portion of the proceeds from their sale to cancer-related causes.

Zimmerman competed against several area men for the title by raising funds for the Leukemia & Lymphoma Society. Each dollar donated toward a candidate’s campaign counted as one vote.  

Zimmerman’s campaign raised $75,000—$30,000 more than his original goal—as a total of $140,000 was raised by all candidates in the 2010 Man and Woman of the Year campaign.

“I’d like to extend my heartfelt appreciation to everyone who donated or volunteered during the Man and Woman of the Year campaign,” Zimmerman says. “The real winners are the people of all ages who benefit from the efforts of the Leukemia & Lymphoma Society. I can’t think of a cause more worthy than the fight against cancer.”

Zimmerman also thanked Stacy Forst, a physician assistant at Fort Wayne Medical Oncology and Hematology, who served as his campaign manager. “Stacy did just an outstanding job,” Zimmerman says.

Zimmerman is competing against several area men for the title of Man of the Year. Each dollar donated toward his campaign counts as one vote and goes to the Leukemia & Lymphoma Society to support cutting-edge cancer research. Whoever receives the most votes—and generates the most money for research—will be Man of the Year.

And you can help him earn that honor—and help fight cancer at the same time.

Zimmerman’s goal is to raise $45,000 by Friday, April 30. The Man of the Year will be announced during the Grand Finale Auction at Sycamore Hills Golf Club on May 1.

“As an oncologist, I’m aware of the devastating effects of blood cancer on both patients and their families,” Zimmerman says. “Every four minutes someone new is diagnosed with a blood cancer. Every 10 minutes someone dies from a blood cancer. The Leukemia and Lymphoma Society is dedicated to funding blood cancer research and providing education and patient services. The society’s mission is to cure leukemia, lymphoma, Hodgkin’s disease, and multiple myeloma, as well as improve the quality of life of patients and their families.”

You can vote (donate) online on his fundraising page.

Zimmerman joined Fort Wayne Medical Oncology and Hematology in 2006. An Indiana native, he completed his residency in hematology and oncology at St. Vincent Hospital in Indianapolis and a fellowship in hematology and oncology at St. Louis University. Before joining Fort Wayne Medical Oncology and Hematology, Zimmerman was in practice for three years in Indianapolis.

After earning a bachelor’s degree at Wabash College in Crawfordsville, Indiana, Zimmerman graduated from the Indiana University School of Medicine. He is board certified in internal medicine and in hematology and oncology.

On Wednesday, November 25 (the day before Thanksgiving), Babu and Leslie Edgar, RN, CS, NP, research coordinator, were able to make contact and arrangements with Alexion Pharmaceuticals to begin the regulatory process necessary to offer Eclulizumab, an investigational drug, to a 19-year-old female diagnosed with relapsed atypical hemolytic-uremic syndrome.

Atypical hemolytic-uremic syndrome (aHUS) is a serious, life-threatening condition that causes hemolytic anemia, thrombocytopenia, and kidney failure. The disease is very rare, with only three per million in children younger than 18. The incidence in adults is even rarer. Prognosis is typically poor, with most patients either dying or going into end-stage renal failure within a year of diagnosis. Babu’s patient was already on kidney dialysis and requiring blood and platelet transfusions. She had originally been diagnosed in February 2009 with the birth of her first child, but had recently relapsed and required hospitalization. She had already received standard treatment for the condition in February.

Babu determined that a new monoclonal antibody, Eculizumab, was undergoing trials in adult patients with plasma-resistant aHUS. Contact was made with Alexion Pharmaceuticals, and over the Thanksgiving holiday, regulatory documents were forwarded by Angela Hamman, data management, to Edgar.      Contacts were made over home phones and by e-mail. The Western Institutional Review Board amazingly agreed to review the trial on Monday. The study “SWAT team” flew to Fort Wayne Sunday evening and arrived at our Lutheran Hospital office Monday morning to begin the patient screening process. The south office lab and pharmacy handled the pressure and extra work gracefully and without complaint. Carrie Boots, RN, NP, and Babu juggled their schedules with the help of Deborah Meyer-Vilensky, RN, to ensure that the patient and the study team were satisfied. Treatment began successfully on Tuesday, and the patient is currently doing very well and improving. 

The typical industry study startup time is at least four weeks, and includes the preparation of documents, Institutional Review Board (IRB) approval, and the signing of the contract and budget. Even though we’re still tying up loose ends and trying to work through the expedited process, the research department needs to be commended for going the extra mile to ensure that the patient was given the appropriate treatment to promote the best possible outcome possible. 

Overview

Cancer is the result of genetic abnormalities that affect the function of particular genes. Genes determine the form, function, and growth patterns of cells. Those that accelerate or suppress growth are often involved in cancer. For example, many cancers have an abnormality in a gene that is responsible for stimulating cellular growth and/or the gene that normally prevents cancer is not working properly. Both of these genetic abnormalities can result in uncontrolled and excessive cellular growth, the hallmark trait of cancer. Genomic tests, or assays as they are called by scientists, are a tool for identifying the specific genes in a cancer that are abnormal or are not working properly. In essence, this is like identifying the genetic signature or fingerprint of a particular cancer.

Genomic testing is different from genetic testing. Genetic tests are typically used to determine whether a healthy individual has an inherited trait (gene) that predisposes them to developing cancer. Genomic tests evaluate the genes in a sample of diseased tissue from a patient who has already been diagnosed with cancer. In this way, genes that have mutated, or have developed abnormal functions, are identified in addition to those that may have been inherited.

Genomic testing can help doctors to:

• Determine a patient’s prognosis (potential outcome)
• Determine whether a cancer is aggressive/fast growing or slow growing
• Choose the most effective treatment for each individual cancer
• Monitor patients who are undergoing treatment to determine if the treatment is working
• Monitor patients who are in remission to catch a potential disease progression early when it is more treatable

Perhaps the greatest promise of genomic testing is its potential for individualizing treatment. This means that patients with more serious conditions can be identified and offered aggressive and innovative therapies that may prolong their lives, while patients who are diagnosed with a less serious condition may be spared unnecessary treatments. For example, some women with node-negative breast cancer will relapse after being treated with surgery alone. Genomic testing has been shown to differentiate between which node-negative breast cancer patients are more likely to relapse and therefore benefit from additional chemotherapy and which patients may not need chemotherapy.

To appreciate how the science of genetics is applied to the diagnosis and monitoring of cancer, it is helpful to have an understanding of the basic principles of genetics. This includes knowing what DNA, chromosomes, and genes are, how they work, and how the information contained in DNA is transformed, through gene expression, into specific structures that dictate the functions of a cell.

With this background knowledge, it is possible to understand the promise of tests for detecting genetic abnormalities, such as:

• Fluorescence in situ hybridization (FISH)
• Polymerase chain reaction (PCR)
• Reverse transcription PCR
• Microarray technology
• Serum proteomics

Background—Basic Principles of Genetics

The importance of genetics in heredity is well known; however, the role that genetics plays in controlling the structure and function of cells may be even more critical for an individual organism. Heredity assures that humans and all species are able to reproduce and perpetuate their unique traits and directing how cells are built, what work they do, and how they grow is necessary to ensure that an organism will survive to reproduce. An understanding of this critical role that DNA and genes have in determining the minute-by-minute life of a cell is also important for understanding how genetics are involved in cancer.

DNA: The genetic information for an entire organism is contained in the nucleus of every cell in the form of deoxyribonucleic acid, commonly known as DNA. DNA is a double-stranded helical (coiled) molecule. Each strand is composed of a structural backbone plus a sequence of nitrogen-containing compounds called nitrogenous bases, which can be thought of as the alphabet of genetics. There are four bases: adenine, guanine, thymine, and cytosine. The two strands are connected at the bases.

The genetic code, or the genetic information that controls structure and function of the cell, is contained in the sequence of bases. The base sequence eventually controls the sequence of amino acids that are connected together to make a protein molecule. Different sequences make different proteins. The proteins that are synthesized in a cell determine the structure and function of that cell.

Chromosomes: DNA is packaged in a specific number of units called chromosomes. Humans have 46 chromosomes in each cell. Most of the time, the chromosomes are packed tightly around proteins in the nucleus of the cell so that they cannot be seen. However, in the stages of the cell’s life just before cell division, the chromosomes become visible with a light microscope. They appear like a capital ‘H’ with four lengths of coiled DNA joined by a protein as the “cross” of the “H”.

Genes: DNA is organized into genes, which are long segments of DNA that include regions that contain codes for proteins called exons, as well as non-coding regions called introns. Genes are defined as the basic unit of heredity because they are passed to offspring and then replicated and passed on to individual cells during cell division. Replication involves using both strands of DNA as templates to synthesize complimentary DNA (cDNA), which is a matching strand. The result is two identical copies of DNA for each cell after cell division is complete. Under normal conditions, the structure of DNA, and thus genes, remains relatively constant through replication and cell division.

Gene expression: The genetic information contained in genes is translated into cellular structure and function through a process called gene expression. Genes can be thought of as codes, or recipes, for making proteins. Proteins are the basic component of cell structure and function. When a gene is “expressed,” the protein or proteins that it codes for are actively being built in the cell and the function that those proteins serve are being performed. For example, when the HER-2/neu gene is expressed in breast cancer, there are more epidermal growth factor receptors (EGFRs) present, which are proteins on the cell surface that HER-2/neu codes for. Furthermore, the function of EGFR is to stimulate cell growth; so a cell that is expressing HER-2/neu has many EGFRs and is actively growing.

Gene expression occurs through a complex system that involves the following steps:

• Temporary separation of the two strands of the DNA molecule at a particular gene.
• Transcription of the segment of DNA, which is the synthesis of a single-stranded copy of the DNA sequence that is exposed; this copy is called messenger RNA (mRNA).
• Protein synthesis, or building new proteins in the cell, based on the information contained in the mRNA.

Genetic abnormalities: Genetic abnormalities are alterations in the DNA of a cell that may occur by chance or due to an environmental influence. These alterations lend the affected cell some advantage over normal cells that helps them grow. As a result, the cell is able to divide rapidly, becoming a cancer growth. However, this growth advantage only benefits the individual cell, and not necessarily the whole organism (human).

Types of genetic abnormalities include:

Translocations—the changing places of a gene from one chromosome with a gene on another chromosome; this type of abnormality defines the many different leukemias

Deletions—a gene or sequence of nucleotides is missing in the DNA

Polymorphisms—variations in nucleotide sequence

Tests for Detecting Genetic Abnormalities

A variety of new laboratory tests can detect genetic abnormalities. Finding a disease-causing mutation in a gene can confirm a suspected diagnosis of cancer or identify those predisposed to certain cancers. Some of these techniques that are currently used in the clinical setting include:

• Fluorescence in situ hybridization (FISH)
• Polymerase chain reaction (PCR)
• Reverse transcription PCR

Furthermore, the following laboratory techniques are being used in cancer research and may be available for clinical use in the future:

• Microarray

Fluorescence in situ hybridization (FISH)

FISH is a laboratory technique that is used to detect genetic abnormalities at the single-cell and single-gene level, such as numerical abnormalities (gains and losses of nucleotides), and translocations (the changing places of a gene or segment of genes on one chromosome with gene or a segment on another chromosome). These abnormalities play a role in the development and progression of some cancers, such as leukemias and lymphomas[1].

How does FISH work? FISH is performed on sample cells whose DNA has unraveled so that the individual chromosomes are visible. This happens during cell phases just before cell division, called metaphase or interphase. The sample DNA is first denatured using heat and the chemical formamide so that the individual strands separate, exposing the base sequence. Next, specific DNA sequences, called probes, that are attached to colored fluoros are incubated, or combined, with the sample DNA. The probes hybridize (connect) with the DNA in the chromosomes that is the compliment to the base sequence in the probe. The presence or absence of fluorescence from the hybridized DNA and probe are visible with a specialized microscope and indicate whether the DNA sequence of interest is present in the sample. Furthermore, specialized FISH techniques can be used to detect translocations, inversions, and amplifications that are involved in cancer.[2]

FISH in breast and ovarian cancer: A common use if FISH is to determine whether patients with breast and ovarian cancer overexpress the HER2/neu oncogene, a gene that is commonly involved in cancer. HER2/neu carries the genetic code for the HER2 receptor, a protein on the surface of some cancer cells. HER2 binds with growth factors in the blood, thereby stimulating cancer cells to grow.

HER2/neu is amplified in approximately 20% to 30% of breast and ovarian cancers and this amplification and/or overexpression indicates a poor prognosis.[3] FISH can be used to observe whether the HER2/neu oncogene is sending multiple signals at the level of the individual cells, which indicates gene amplification.

FISH in hematological (blood) cancers: FISH may also be used to diagnose and manage various hematological malignancies. The genetic abnormality that underlies many hematological malignancies is chromosomal translocation, or the changing places of gene from one chromosome with a gene on another chromosome.

Polymerase chain reaction (PCR)

PCR is an in vitro laboratory method that is useful for genetic testing for disease and detecting minimal residual disease, which is a small amount of disease left after treatment that may lead to recurrence and is typically not detectable with other techniques. This procedure amplifies a segment of DNA from a small sample, making it detectable. With PCR, relatively small sequences of known DNA can be replicated into millions of copies over a short period of time.

How does PCR work? This method requires four principle components: 1) the sample DNA, 2) an ample supply of nucleotides, 3) a heat-stable polymerase enzyme which is responsible for copying DNA, and 4) primers, short sequence of nucleotides that lie on either side of the DNA fragment of interest and signal the polymerase to begin replication of the specific DNA segment.

PCR is a three-step process, each occurring at a different temperature. The sample DNA is first heated to approximately 90ºC in order to separate the 2 paired DNA strands. Once separated, it is cooled to a temperature that allows the primers to hybridize to their complementary sequence on the target DNA, approximately 40ºC. Lastly, DNA replication occurs at approximately 70ºC, the temperature at which DNA polymerase is most active. This process is repeated 20 to 30 times, resulting in approximately 1 million-fold amplification of the DNA fragment of interest.[4]

Reverse transcription PCR

Reverse transcription (RT)-PCR is a technique that detects the degree to which genes are expressed. Complicated processes control which segment of DNA separates, gets transcribed (copied) into mRNA, and then expressed as proteins in the cell. Not all genes are transcribed and then expressed equally. Due to many controls in the cell, some genes are over-expressed, which means they are transcribed and expressed at a higher rate than normal, while other genes are now expressed, or “turned off” so that certain functions are not manifested in the cell.

How does RT-PCR work? RT-PCR uses the same steps as PCR to amplify a segment of DNA, but the sample is a complimentary copy of mRNA. By starting with mRNA, this test measures only the DNA that is expressed, making it possible to determine the degree to which certain genes are expressed. Recent uses of RT-PCR in clinical oncology include detection of lymph node micrometastases in prostate cancer and bone metastases in breast cancer.[5]

RT-PCR in breast cancer: The breast cancer test Oncotype DX™ utilizes RT-PCR to determine the individual risk of recurrence in women with node-negative estrogen receptor (ER)-positive breast cancer. This test evaluates expression of 21 genes in breast cancer. Overexpression of some of these genes indicates a worse prognosis, while expression of others may indicate a better prognosis. The expression of all 21 genes is used to calculate a “Recurrence Score™”, or the likelihood that that cancer will recur. A large clinical trial showed that Recurrence Score™ was more effective for predicting prognosis of women with node-negative, ER-positive breast cancer than standard measures such as patient age, cancer size, and cancer stage.[6]

Strategies to Improve Detection of Genetic Abnormalities

Several methods for detecting genetic abnormalities are being utilized for cancer research. While they are not yet routinely used in the clinical setting, the following appear to be promising and may be used in the future for diagnosing, testing, and monitoring cancer.

Microarrays: Microarray analysis is a technique that combines biology with computer science to generate a genetic profile for a given tissue sample that reflects the activity of thousands of genes. This technology has advantages over FISH or PCR because, in a single analysis, it can evaluate the expression of all of the genes that may be involved in a cancer, rather than just a few. By graphically showing how all of the genes are involved in a cancer, microarrays can generate a “genetic signature” for a particular cancer. This makes the identification of cancer subtype more precise. The ability to take a snapshot of a cancer’s genetic signature may lead to a better understanding of how that cancer develops and how to design individualized treatment.

How do microarrays work? While different microarray methods are utilized, each consists of five basic steps:

• Preparation of the sample
• Combining the sample with the computer chip
• Scanning the computer chip
• Normalization
• Computer analysis of the results.

Preparation of the sample: In the initial step, cDNA is synthesized from RNA by reverse transcription (remember transcription involves copying DNA to make RNA, so reverse transcription is generating DNA from RNA) from RNA that has been extracted from both a test and a reference sample. The sample DNA segments are labeled with fluorochromes, or radioactive chemicals, so that they can be detected after they combine with the computer chip.

Combining the sample with the computer chip: Next, the sample is combined with the computer chip, which is a rectangular grid of spots. Each spot has many copies of a particular DNA sequence. These sequences are derived from public databases of DNA sequences that were generated through the Human Genome Project, the scientific endeavor that identified virtually all of the DNA sequences in the human species.

When the sample is added to the computer chip, a process called hybridization occurs. This means that the sample DNA segment binds (hybridizes) to the segment on the computer chip that has the exact complimentary sequence of nucleotides (the four compounds that are the alphabet of genetics).

Scanning the computer chip: Once hybridization is complete, scanners are used to detect the fluorescence and create a digital image that reflects where the sample DNA combined with spots on the microarray chip.

Normalization: Because raw signal intensities may vary between individual chips from many patients or experiments, individual chip intensity must be adjusted to a common standard, or normalized. For example, subtraction of background noise is a common normalization method that is applied to all samples. Normalization makes it possible to compare gene expression profiles from many patients or experiments.

Computer analysis: The final step in a microarray experiment is computer analysis. The thousands of raw data points that result from microarray analyses are essentially unintelligible unless they are evaluated in the context of other results. For example, the gene expression profile (microarray results) of normal and diseased tissue can be compared to identify genes that vary in their expression and also identify a pattern (profile) that may indicate a distinct class or stage of disease.[7]

Microarrays in oncology: Microarray analysis has contributed to oncology by increasing an understanding of the genetic basis of several types of cancer, including B-cell non-Hodgkin’s lymphoma (BCNHL), acute leukemia, and breast cancer.

• Considerable knowledge regarding the pathology of BCNHL has been gained by comparing gene expression patterns of diseased and normal tissue. Two different disease categories display distinct gene expression profiles. Microarrays have helped establish these expression profiles and, in the future, they may help accurately classify new cases of BCNHL.
• In the case of acute leukemia, microarrays have helped establish distinct gene expression patterns that have helped differentiate acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). Using these profiles, 29 of 34 new cases of leukemia were correctly predicted.
• Furthermore, microarrays have helped identify two distinct gene expression profiles in breast cancer, BCRA1 and BCRA2. This finding suggests different ways that breast cancer develops and provides clues that promote further understanding of the cause of breast cancer.[7]

References

[1] Spagnolo SD, Ellis DW, Juneja S, Leong AS, et al. The role of molecular studies in lymphoma diagnosis: a review. Pathology 2004; 36 (1)19-44.

[2] Spurbeck JL, Adams SA, Stupca PJ, Dewald GW. Primer on Medical Genomics Part XI: Visualizing Human Chromosomes. Mayo Clinic Proceedings 2004:79:58-75.

[3] Paik S, Hazan R, Fisher ER, et al. Pathological findings from the national surgical adjuvant breast and bowel project: prognostic significance of erb B-2 protein overexpression in primary breast cancer. J Clin Oncol 1990;8:103-112.

[4] Tefferi A, Wieben ED, Dewald GW, et al. Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics. Mayo Clinic Proceedings 2002;77:785-808.

[5] Tefferi A, Wieben ED, Dewald GW, et al. Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics. Mayo Clinic Proceedings 2002;77:785-808.

[6] Paik S, Shak S, Tang G, et al. Multi-gene PT-PCR assay for predicting recurrence in node negative breast cancer patients—NSABP studies B-20 and B-14. Proc of the 26th Annual San Antonio Breast Cancer Symposium. December 3-8k, 2003; San Antonio, TX, Abstract #16.

[7] Tefferi A, Bolander ME, Ansell SM, et al. Primer on Medical Genomics Part III: Microarray Experiments and Data Analysis. Mayo Clinic Proceedings 2002;77:927-940.

Tumor markers are often used to:

• Monitor response to treatment—some tests show whether the cancer is responding to treatment
• Monitor for progression—in general, an increase in some tumor markers indicates disease progression
• Detect recurrence—regular monitoring of some tumor markers during a remission may help detect recurrence
• Detect metastasis—metastasis is the spread of cancer from its site of origin to another distant location in the body
• Screen at-risk individuals—Prostate specific antigen is an example of a tumor marker that is specific enough for one condition—prostate cancer—to function as a screening test for asymptomatic, at-risk men, which generally refers to men over 50 years of age with at least a 10-year life expectancy.
• Identify specific cancer subtype—some cancers are divided into subtypes that are more or less aggressive; some tumor marker tests make it possible to distinguish between cancer types
• Predict prognosis—test results may indicate the chance of a negative or positive outcome, based on outcomes of other patients with similar results

Tumor markers are not specific enough to be used alone for diagnosing cancer. There are several reasons for this:

• Tumor marker levels can be elevated in people with benign (non-cancerous) disease.
• Tumor markers are not elevated in every person with cancer, particularly those with early stage disease.
• Most tumor markers are not totally specific for a single condition, meaning that many different cancers or diseases can result in a higher than normal level of a particular marker.

For these reasons, tumor markers are not used in isolation; instead, results from tumor marker tests are evaluated in the context of a patient’s history, symptoms, and other test results.

Despite these limitations, researchers continue to study the markers in table 1, as well as potential new markers to determine whether they may have a role in screening, early detection, and directing treatment.

Table 1: Tumor markers by cancer type

New advances in tumor marker tests: Most tumor markers are proteins. Since DNA is the code that determines which proteins will be produced by a cell, researchers are developing methods to detect DNA. Even in many early stage diseases, cancer cells may break away from the tissue where they originated and can be detected in the blood or other body substances. For example, researchers have detected abnormal DNA in the:

• Blood of people with breast, liver, lung, ovarian cancer, and melanoma
• Urine of individuals with bladder cancer
• Saliva of individuals with cancers of the oral cavity

This new approach to tumor marker testing can be thought of as measuring the cause (DNA) rather than the effect (protein), and may thus provide even more accurate and useful information for screening, early detection, monitoring, and planning treatment.

Researchers from Italy have found that measuring circulating DNA appears to be an accurate and quick method of detecting lung cancer, even in its earliest stages. This trial involved 100 patients who had been newly diagnosed with lung cancer, with stages I – IV (earliest stage to most advanced stage). Blood was drawn and tested for DNA in 100 patients who had been newly diagnosed with lung cancer (stages I-IV) and compared blood drawn from control groups, which included:

• Individuals who were heavy smokers but did not have lung cancer, and
• Individuals who were not smokers and did not have lung cancer.

DNA levels in the blood were 8 times higher in patients with lung cancer, compared to the control group. These levels were also detected in individuals with early-stage cancer. Only patients with cancer had high levels of DNA in their blood. Elevated DNA accurately detected lung cancer in 90% of cases.[1]

References

[1] Sozzi G, Conte D, Leon M, et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. Journal of Clinical Oncology 2003;21:3902-3908.

Blood tests are used to measure the number of blood cells in circulation and the levels of chemicals, enzymes, proteins, and organic waste products that are normally found in the blood. The levels of blood cells, such as red blood cells, white blood cells and platelets, may be low in patients receiving treatment for cancer. Also, the levels of some chemicals normally found in the blood may be either too high or too low as a result of the cancer or its treatment. There are two types of blood tests typically performed during cancer treatment: the complete blood count (CBC) and a blood chemistry panel.

Complete Blood Count (CBC)

The CBC measures the levels of the three basic blood cells: red blood cells, white blood cells, and platelets. In the United States, the CBC is typically reported in the format shown in Table 1 below. It is important to understand not only which blood counts are being tested, but also how those results are reported. You will want to pay careful attention to the results column, which shows any results that are normal and the flag column, which shows any results that are abnormal.

Table 1: CBC with results and reference interval

Result column: The result column shows counts that fall within the normal range.

Flag column: The flag column shows counts that are lower (”L”) or higher (”H”) than the normal range.

Reference interval (or reference range) column: The reference interval shows the normal range for each measurement for the lab performing the test. Different labs may use different reference intervals.

White blood cells: White blood cells help protect individuals from infections. The above CBC report shows that the patient’s total white cell count is 1.5, which is lower than the normal range of 4.0-10.5. The low white cell count increases the risk of infection.

Absolute neutrophil count: Neutrophils are the main white blood cell for fighting or preventing bacterial or fungal infections. In the CBC report, neutrophils may be referred to as polymorphonuclear cells (polys or PMNs) or neutrophils. The absolute neutrophil count (ANC) is a measure of the total number of neutrophils present in the blood. When the ANC is less than 1,000, the risk of infection increases. The ANC can be calculated by multiplying the total WBC by the percent of polymorphonuclear cells. For example, this patient’s ANC is 0.34, which equals (WBC) 1.5 x 23%.

Red blood cells: Red blood cells carry oxygen from the lungs to the rest of the body. The above CBC report indicates that the patient has a red cell count of 3.5, which is lower than the normal range of 4.70-6.10, and therefore, shown in the flag column.

Hemoglobin (Hb or Hgb): Hemoglobin is a protein in the red cell that carries oxygen. The above CBC report indicates that the patient’s Hb count is 10.8, which is below the normal range of 14.0-18.0. The hematocrit (HCT), another way of measuring the amount of Hb, is also low. This means that the patient has mild anemia and may be starting to notice symptoms.

Platelets: Platelets are the cells that form blood clots that stop bleeding. The above CBC report indicates that the platelet count for this patient is normal.
Blood Chemistry Panel

The blood chemistry panel measures the levels of chemicals, enzymes, and organic waste products that are normally found in the blood. The results of a blood chemistry panel are typically reported with the name of the substance, the result, and the reference interval, as shown in Table 2. The reference interval is the normal range for that laboratory. Reference intervals may vary between laboratories. Substances that are typically measured in cancer patients are as follows:

Table 2: Sample blood chemistry panel with results and reference interval

Albumin is the most prevalent protein in the blood. It is synthesized in the liver and removed from circulation by the kidney, which causes it to be excreted in the urine. Albumin is often measured in order to detect liver damage or kidney damage, either of which may be a side effect of cancer or cancer treatment.

Alanine aminotransferase (ALT) is an enzyme in the liver that rearranges the building blocks of proteins. It is released from damaged liver cells. Cancer patients may experience liver damage as a side effect of some cancer treatments or due to spread of cancer to their liver. ALT may also be referred to as SGPT (serum glutamic pyruvic transferase.)

Aspartate aminotransferase (AST) is an enzyme in the liver that rearranges the building blocks of proteins. It is released from damaged liver cells. Cancer patients may experience liver damage as a side effect of some cancer treatments or due to spread of cancer to their liver. AST may also be referred to as SGOT (serum glutamic oxaloacetic transaminase.)

Alkaline phosphatase is an enzyme is that involved in bone growth. It is processed in the liver and excreted into the digestive tract in the bile. A higher than normal amount of alkaline phosphatase indicates bone or liver problems. In cancer patients, elevated alkaline phosphatase may indicate that cancer has spread to the bones or that liver damage, possibly due to some chemotherapy drugs, has caused problems with bile excretion.

Billirubin is a substance that is formed from broken down red blood cells. It becomes part of bile, which is produced by the liver. A build-up of bilirubin can cause jaundice and may be measured to test for liver or bile duct function, which may be compromised if there is cancer in the liver or if there is liver damage. Some chemotherapy drugs may cause liver damage.

BUN (blood urea nitrogen) is a part of urea, the waste product that is left over from the breakdown of protein. Urea circulates in the blood until it is filtered out by the kidneys and excreted in the urine. If the kidneys are not functioning properly, there will be excess urea in the bloodstream, resulting in higher than normal BUN levels. Cancer patients may have elevated BUN if they have been treated with certain chemotherapy drugs that may cause kidney damage.

Calcium is a chemical that is necessary for muscle contraction, nerve function, blood clotting, cell division, healthy bones and teeth. An increased level of calcium in the bloodstream is a possible complication of cancer and is referred to as hypercalcemia. In its severe form, hypercalcemia may be a life-threatening emergency.

Chloride is a chemical that helps maintain fluid balance in the body. Low chloride levels may be caused by vomiting or diarrhea.

Creatinine is a compound that is produced by the body and excreted in the urine. Compounds that leave the body in the urine are processed by the kidney, therefore creatinine may be used to monitor for kidney function. Some cancer treatments may cause kidney damage.

Glucose is the simplest form of sugar that the body uses for energy. The body requires insulin to move sugar from the bloodstream into the cells for energy production. An abnormal glucose reading may signify a problem with insulin production, which occurs in the pancreas.

Lactate dehydrogenase (LDH) is involved in producing energy and is released from damaged cells in many areas of the body, including the heart and liver. Cancer patients may have an elevated LDH due to spread of cancer to their liver or damage to their liver from certain cancer treatments. For more information, go to Liver Damage. LDH is also considered a tumor marker, which is a substance that occurs at higher than normal amounts in the presence of cancer.

Magnesium is a chemical that is necessary for muscle contraction, nerve function, heart rhythm, bone strength, generating energy, and building protein.

Potassium is a chemical that regulates heart contraction and helps maintain fluid balance. Low sodium levels may be caused by vomiting or diarrhea.

Sodium is a chemical that helps maintain fluid balance and is necessary for muscle contraction and nerve function. Low sodium levels may be caused by vomiting or diarrhea.

Uric Acid is the end product of the digestion of certain proteins and is normally eliminated through the urine. Excess uric acid may be a side effect of some cancer treatments, and may lead to a condition called tumor lysis syndrome. When excess uric acid is present, it is converted to crystal. These crystals may be deposited in the tiny tubes that are part of the kidney and cause acute kidney damage, which can ultimately lead to kidney failure.

Additional results that are sometimes included in the blood chemistry panel are measures of the blood’s clotting capacity. Some cancer treatments reduce the number of platelets in circulation, which can cause the blood to clot more slowly so that the patient is more susceptible to excessive bleeding.

Table 3: Measures of the blood’s clotting capacity

Activated Partial Thromboplastin Time (aPTT) is a measure of bleeding and clotting and is used to evaluate unexplained bleeding or monitor heparin treatment. Heparin is a drug that is administered to increase the clotting capacity of a patient’s blood. Some cancer patients may receive heparin as treatment for a low platelet count, or thrombocytopenia, which is a side effect of some cancer treatments. This condition can lead to more easy bruising and bleeding.

Prothrombin time (PT) is the most common way to express the clotting capacity of blood. PT results are reported as the number of seconds the blood takes to clot when mixed with a thromboplastin reagent. The International Normalized Ratio (INR) was created by the World Health Organization because PT results can vary depending on the thromboplastin reagent used. The INR is a conversion unit that takes into account the different sensitivities of thromboplastins. The INR is widely accepted as the standard unit for reporting PT results. Cancer patients may have an abnormally low PT/INR due to a lower than normal platelet count. Platelets are the components of blood that stop bleeding by clotting the blood. A low platelet count, also called thrombocytopenia, and a low PT may lead to more frequent bruising and bleeding.

• Radiography (x-ray)
• Bone Scan
• Bone Survey
• Dual Energy X-ray Absortiometry (DEXA) Scanning
• Mammography
• Ultrasound
• Positron emission tomography (PET) scan
• Magnetic resonance imaging (MRI)
• Computed tomography (CT) scan
• Combined CT/PET scan

Radiography (x-ray): Radiography involves the use of radiation (x-rays) to create an image of the body. Radiographs are created by passing small, highly controlled amounts of radiation through the human body, capturing the resulting image on a special type of photographic film. Radiation passes through the various structures of the body differently. For example, very little radiation passes through the bones, leaving white “shadows” on the x-ray film. This is why X-rays are very useful for evaluating bones, as in detecting fractures.

X-rays are useful for determining whether cancer has spread (metastasized) to the bones. Because cancer cells are so dense and metabolically active, tumors, or masses of cancer cells, may also appear white on an x-ray, as is the case with lung cancer.

Bone scan: A type of x-ray called a bone scan may be performed to diagnose cancer in the bones or bone metastases. In this test, low level radioactive particles are injected into a vein. They circulate through the body and are selectively picked up by the bones. A high concentration of these radioactive particles indicates the presence of rapidly growing cancer cells in the bones.

Skeletal survey: A skeletal survey may be performed to diagnose cancer in the bones that causes extra build-up of bone, called blastic lesions. A skeletal survey is a type of X-ray. Conventional X-rays are used to image small sections of the body that may be of concern, such as the spine; whereas skeletal surveys image all areas of the body.

Dual Energy X-ray Absortiometry (DEXA) Scanning: DEXA scanning is the most widely used method for measuring bone mineral density. Bone density may weaken with bone metastases, cancer that has spread to the bones, or with osteoporosis, a weakening of the bones related to aging. DEXA scanning rapidly directs x-ray energy, alternating from two different sources, through the bone being examined. Once the x-rays have passed through the bone, their strength is recorded. Bone density or bone loss is calculated from the amount of energy that travels through the bone and is picked up by the detector. The minerals in bone, predominantly calcium, weaken the transmission of the x-rays through the bone. The more dense the bone is, the less x-rays get through to the detector. The use of two different x-ray energy sources greatly improves the precision and accuracy of the measurement.

Mammography: Mammography uses safe, low doses of X-rays to image the inside of the breast. During a mammogram, the breast tissue will be compressed with a smooth plastic shield in order to help produce a highly detailed image. The X-rays pass through the breast and form an image on the X-ray film. Typically, two or three images are made of each breast.

Ultrasound (sonography): Ultrasound uses high frequency sound waves and their echoes to create an image. The primary advantage of ultrasound is that internal organs and other structures can be observed without using radiation. The ultrasound machine transmits sound pulses into the body using a probe. The sound waves travel through the body until they hit a boundary between tissues (e.g. between fluid and soft tissue, soft tissue and bone). At the boundary, some of the sound waves get reflected back to the probe, while some travel on further until they reach another boundary and get reflected. The reflected waves are detected by the probe and relayed to the machine, which calculates the distance from the probe to the tissue or organ. The machine displays the distances and intensities of the echoes on the screen, forming a two-dimensional image.

Newer ultrasound machines are capable of creating three-dimensional images. In these machines, several two-dimensional images are acquired by moving the probes across the body surface or rotating inserted probes. The two-dimensional scans are then combined by specialized computer software to form 3D images. 3D imaging allows the physician to see the organ being examined better, and is often used for early detection of cancer in the prostate, colon, rectum, and breast.

Ultrasound that is enhaced with the use of additional technologies appears to be even more effective for detecting cancer. A new development in ultrasound involves the use of color Doppler imaging. Doppler imaging is a technique that can detect differences in velocity (i.e. blood flow versus solid tissue) and transmits these differences in the form of different colors on a screen. This technique allows physicians to better determine the presence and exact location of a mass within the body.

Another type of ultrasound is microbubble-enhanced color Doppler, which has been shown to improve the detection of some cancers and reduce unnecessary biopsies compared to color Doppler that is not enhanced. Microbubbles are tiny bubbles of gas that can permeate through small blood vessels without causing harm. Since blood vessels and blood flow are more prevalent in cancerous tissues than regular tissues, microbubbles tend to concentrate in the cancer, which is revealed on the ultrasound image. This allows physicians to more accurately locate where to do the biopsy.

Positron emission tomography (PET): Unlike techniques that provide anatomical images, such as X-ray, CT and MRI, PET scans show chemical and physiological changes related to metabolism. This is important because these functional changes often occur before structural changes in tissues. PET images may therefore show abnormalities long before they would be revealed by X-ray, CT, or MRI.

Before a PET scan, a patient will receive an injection of a radiopharmaceutical, which is a drug labeled with a basic element of biological substances, called an isotope. These isotopes distribute in the organs and tissues of the body and mimic natural substances such as sugars, water, proteins, and oxygen. This radioactive substance is then taken up by the cancer cells, thereby allowing the radiologist to visualize areas of increased activity.

After the patient has received the injection, a small amount of radiation is passed through the body, which detects the isotopes and reveals details of cellular-level metabolism. Although the radiation is different from that used in radiography, it’s roughly equivalent to what is administered in two chest x-rays. After the scan is complete the radiation does not stay in the body for very long.

PET is useful for diagnosing lung and breast cancer, and for monitoring response to therapy. Effective therapy leads to rapid reductions in the amount of glucose that is taken up by tumors. PET imaging can easily reveal this drop in metabolic activity and show—sometimes within minutes or hours—whether a patient is responding positively to a particular course of treatment. PET has been shown effective for predicting outcomes, detecting spread of cancer, and/or monitoring therapeutic response in a wide range of cancers, including breast, colon, lung, ovarian, head, neck, and thyroid cancers, as well as melanoma and lymphoma.

Magnetic resonance imaging (MRI): MRI uses a strong magnet and radiofrequency waves to produce an image of internal organs and structures. Under the influence of the strong magnet, the hydrogen atoms in the body line up like compass needles. Next, the patient is exposed to radio waves that cause the hydrogen atoms to momentarily change positions. In the process of returning to their orientation under the influence of the magnet, they emit a brief radio signal. The intensity of these radio waves reflects what type of tissue exists in that area of the body. The MRI system goes through the area of the body being imaged, point by point, collecting information from how the radio waves emit. A computer generates an image of organs and structures based on these radio wave recordings.

MRI has proven useful for detecting some types of cancer, and in some cases, may be more effective than biopsy, mammography, or ultrasound.

Computed tomography (CT): A CT scan is a detailed radiograph, or X-ray. The CT imaging system is comprised of a motorized table that moves the patient through a circular opening and an X-ray machine that rotates around the patient as they move through. Detectors on the opposite side of the patient from where the X-ray entered record the radiation exiting that section of the patient’s body, creating an X-ray “snapshot” at one position (angle). Many different “snapshots” are collected during one complete rotation of the X-ray machine. A computer then assembles the series of X-ray images into a cross-section, or a picture of one small slice of the body. A CT scan is a series of these cross-sectional images.

PET/CT combination scan: Recent research indicates that a combination PET/CT scan may be more effective than whole body MRI for diagnosing the extent of spread for various cancers. Researchers from Germany conducted both combination PET/CT and MRI on 98 patients with various cancers. Overall, PET/CT scanning was 77% accurate for detecting the original cancer, cancer spread to nearby lymph nodes, and cancer spread to distant sites in the body, compared with only 53% accuracy with MRI.[1]

References